The long-term effect of clomiphene citrate on vaginal epithelial differentiation in the mouse

Clomiphene citrate, administered to the neonatal mouse during cervicovaginal epithelial differentiation, is associated with subsequent adenosis. Similar lack of neonatal transformation of columnar to squamous epithelium occurs after diethylstilbestrol. Mouse neonatally exposed to diethylstilbestrol have a high incidence of reproductive tract tumors in later life. In this study Balb/c neonates were exposed to clomiphene citrate, maintained with controls, and killed at 52, 56, and 60 weeks. Cervicovaginal histology was studied by light microscopy. In all control animals only mature squamous epithelium was seen (44/44). After clomiphene citrate, at 52 weeks, 3/10 animals had other than mature squamous epithelium identified. One of these genital tracts contained adenosis. At 56 weeks only mature squamous epithelium was seen (11/11), and at 60 weeks immature squamous epithelium was identified in 1 of 10 animals. In no study animal (0/31) was there any evidence of tumor development. This differs from the high incidence of reproductive tract tumor seen in the mouse after neonatal diethylstilbestrol exposure.